OBJECTIVE:To systematically review the effectiveness and safety of methotrexate(MTX)in the treatment of rheuma-toid arthritis,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from Medline,EMBase,Cochrane Library,PubMed,CJFD,CBM,VIP and Wanfang Database,randomized controlled trials(RCT)about MTX in the treatment of rheu-matoid arthritis were collected,Meta-analysis was performed after data extraction and quality evaluation. RESULTS & CONCLU-SIONS:33 effectiveness evaluation were included,involving 8 253 patients,and 53 safety evaluation were included,involving 4 803 patients. Results of analysis show,the efficacy of MTX was not higher than leflunomide in the treatment of rheumatoid arthritis,superi-or to cyclosporine A,and similar to sulfasalazine. In addition,MTX shows similar efficacy with etanercept(7.5-20 mg per week),goli-mumab,adalimumab or rituximab,but less effective than trastuzumab. The incidence of adverse reactions of MTX is high,but mainly mild or moderate,and the most common adverse reactions are gastrointestinal symptoms. Oral administration of MTX is more secure than intramuscular injection and subcutaneous injection.

Objective To explore the correlation between hyperuricaemia and blood pressure, and blood lipid and glucose. Methods By using simple cluster sampling, 2 branch units from PetroChina Changqing Oilfield Company were selected, and all the 720 subjects with hyperuricaemia (HUA) were assigned to the HUA group; another 620 participants with normal uric acid (UA) level into the normal group. The correlation between blood uric acid and blood pressure,and blood lipid and glucose was assessed by Logistic regression. Results The odds ratio (OR) of those who had 1,2 or 3 abnormal status of hypertension,hyperlipidemia and impaired fasting glucose in the HUA group were much higher than the normal group (OR values were 4. 036,2. 562, and 4. 174, respectively). Logistic regression showed that male, systolic blood pressure ( SBP), GLU, total cholesterol ( TC), triglyceride ( TG), low-density lipoprotein cholesterol (LDL-C) were risk factors of H UA ( OR values were 7. 736,2. 309,1.721,2. 761 and 1. 411,respectively) ,while high-density lipoprotein cholesterol (HDL-C, OR = 0. 211 ) was a protective factor of HUA. Conclusions Gender,blood pressure and blood lipid may have correlation with blood UA. Multiple risk factors should be considered to improve the effectiveness of health education and health promotion.

OBJECTIVETo analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage.

METHODSWe measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively.

RESULTSFEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all.

CONCLUSIONThe dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

Adult ; Air Pollutants, Occupational ; urine ; Coke ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Phenanthrenes ; urine ; Polycyclic Aromatic Hydrocarbons ; urine ; Pyrenes ; urine ; Respiratory Function Tests

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI). The primary outcome of our interest was the recurrence of major adverse cardiovascular events (MACE) in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.
Continental Population Groups ; Cytochrome P-450 CYP2C19 ; genetics ; Gene Frequency ; Humans ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Genetic ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Objective:To explore the effects and mechanism of Chinese classical prescription Dahuang Zhechongwan on silicosis in mice. Method:Thirty-six male Kunming mice of SPF grade were randomized into the normal control group， model control group， tetrandrine （Tet， 0.039 mg·kg^-1） group， as well as high- （1.560 g·kg^-1）， medium- （0.780 g·kg^-1）， and low-dose （0.390 g·kg^-1） Dahuang Zhechongwan groups， with six mice in each group. Mice in all groups except for the normal control group underwent static inhalation of silica （SiO₂） dust for 40 consecutive days to induce fibrosis. After 28 days of intervention with corresponding drugs， the mice were sacrificed to collect the serum and lung tissues， with the former used for detecting tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， and hydroxyproline （HYP） levels by enzyme-linked immunosorbent assay （ELISA） and the latter for observing the pathological changes. Meanwhile， the protein and mRNA expression levels of p38 mitogen-activated protein kinase （p38 MAPK）， nuclear transcription factor-κB （NF-κB）， transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， Smad2， Smad3， and Smad7 in the lung tissues were determined by Western blot and real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the contents of TNF-α， IL-1β， IL-6 and HYP in the model group were significantly increased， the difference was statistically significant（P<0.05，P<0.01）； compared with the model group， the high-dose group of Dahuang Zhechongwan could significantly reduce the contents of TNF-α， IL-6 and HYP in the serum of mice（P<0.05， P<0.01）， indicating that Dahuang Zhechongwan could reduce the lung inflammation of silicosis mice. At the same time， compared with the normal group， the protein and mRNA expression levels of p38 MAPK， NF-κB p65， TGF-β₁， α-SMA， Smad2 and Smad3 in the model group were significantly increased（P<0.05，P<0.01）， while the protein and mRNA expression levels of Smad7 were significantly decreased（P<0.01）； compared with the model group， the protein and mRNA expression levels of p38 MAPK， NF-κB p65， TGF-β₁， α-SMA， Smad2 and Smad3 in the high-dose Dahuang Zhechongwan group were significantly increased the protein and mRNA expression levels were significantly decreased（P<0.05，P<0.01）， while Smad7 protein and mRNA expression levels were significantly increased（P<0.05，P<0.01）. Conclusion:Dahuang Zhechongwan ameliorates the alveolar inflammation， extracellular matrix （ECM） deposition， and fibrosis in mice with silicosis possibly by regulating the p38 MAPK/NF-κB/TGF-β₁ pathway.

Objective: To study the expression and effect of small nuclear ribonucleoprotein-associated protein B (SNRPB) on proliferation and metastasis of liver cancer tissues and cells. Methods: The bioinformatics database starBase v3.0 and GEPIA were used to analyze the expression of SNRPB in liver cancer tissue and normal liver tissue, as well as the survival and prognosis of liver cancer patients. The expression of SNRPB mRNA and protein in liver cancer cell lines were analyzed by qRT-PCR and Western blot. RNA interference technique (siRNA) was used to determine SNRPB protein expression down-regulation. The proliferation effect on hepatocellular carcinoma cells was observed by MTT assay. Transwell invasion and migration assay was used to detect the changes in the metastatic ability of liver cancer cells after SNRPB down-regulation. Western blot was used to detect the changes of epithelial mesenchymal transition (EMT) markers in liver cancer cells after down-regulation of SNRPB expression. Data were compared between two groups and multiple groups using t-test and analysis of variance. Results: The expression of SNRPB was significantly higher in liver cancer tissue than normal liver tissue, and its expression level was correlated with the prognosis of liver cancer patients. Compared with the immortalized hepatocyte LO(2), the expression of SNRPB was significantly increased in the liver cancer cells (P < 0.01). siRNA-SNRPB had significantly inhibited the expression of SNRPB mRNA and protein in liver cancer cells. MTT results showed that the absorbance value was lower in SNRPB knockdown group than negative control group, and the difference at 96 h after transfection was most significant (P < 0.01). Transwell assay results showed that compared with the negative control group, the SNRPB knockdown group (MHCC-97H: 121.27 ± 8.12 vs. 46.38 ± 7.54; Huh7: 126.50 ± 6.98 vs. 41.10 ± 8.01) invasion and migration (MHCC-97H: 125.20 ± 4.77 vs. 43.18 ± 7.32; Huh7: 132.22 ± 8.21 vs. 38.00 ± 6.78) ability was significantly reduced (P < 0.01) in liver cancer cells. Western blot showed that the expression level of epithelial phenotype marker E-cadherin was decreased after down-regulation of SNRPB, while the expression levels of mesenchymal phenotype markers N-cadherin and vimentin was increased, suggesting that down-regulation of SNRPB inhibited EMT in liver cancer cells. Conclusion: SNRPB expression is significantly increased in liver cancer tissues and cells, and it is involved in regulating the proliferation, metastasis and EMT of liver cancer cells.
Carcinoma, Hepatocellular/genetics* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms/genetics* ; snRNP Core Proteins

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

OBJECTIVE To explore the effects of the expression of serum Sirtuin-1 （SIRT1） on therapeutic efficacy of sodium valproate （VPA） in the treatment of epilepsy patients. METHODS Fifty-four epileptic patients were collected from the Affiliated Baiyun Hospital of Guizhou Medical University from Mar. to Oct. 2021 as the research objects， and fifty healthy people were also collected during corresponding period as baseline reference samples. The patients whose relative mRNA expression of SIRT1 was lower than the baseline were selected as SIRT1 low-expression treatment group， and the patients whose that expression was higher than the baseline as SIRT1 high-expression treatment group.All patients were treated with low dose （12 mg/kg or about 600 mg/day） of VPA for 3 months， and the clinical efficacy was evaluated. The dosage of VPA in patients with ineffective gzwkj2021-468） epilepsy control should be increased to 15 mg/kg or about 800 mg/day for another 3 months as SIRT1 high-expression intensive treatment group and SIRT1 low-expression intensive treatment group. Clinical efficacies were evaluated. The blood concentration and liver function indexes of the patients were detected after 3 months of treatment and 3 months of intensive treatment. RESULTS Before treatment， among 54 epileptic patients， 31 epileptic patients had low expression of SIRT1， and 23 had high expression of SIRT1. After 3 months of low-dose VPA treatment， within effective blood concentration of VPA， effective control rate of patients in SIRT1 high-expression treatment group was significantly lower than SIRT1 low-expression treatment group （P＜0.05）. After 3 months of intensive treatment， the effective control rate of patients SIRT1 high-expression intensive treatment group was significantly higher than SIRT1 high expression treatment group （P＜0.05）. No abnormality was found in liver function indexes during VPA treatment. CONCLUSIONS Epilepsy in patients with high expression of serum SIRT1 may be more difficult to control when VPA is within the effective blood concentration range； when the VPA dose is effectively increased， the effective control rate of epilepsy can be improved.

AIM:To evaluate the agreement of corneal high-order aberrations from Topcon KR-1W, i.Profiler and OPD-Scan Ⅲ wavefront aberrometers in myopic adults.METHODS:A prospective clinical study. A total of 92 adult patients(92 eyes)with myopia in the department of optometry, the People's Hospital of Guangxi Zhuang Autonomous Region from June to August 2022 were enrolled. The third-order and fourth-order corneal aberrations at the pupil diameter of 4 and 6mm were measured by Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, respectively. The difference and agreement of the three aberrometers were evaluated.RESULTS: The measurements at 6mm pupil diameter were all greater than those at 4mm pupil diameter. Although there were no statistical differences in the measurements of Z-44、Z-24 by the three aberrometers at 4 pupil diameter(P>0.05), there were statistical differences in other measurements(P<0.05). The aberration results measured by the three aberrometers were statistically different at the 6mm pupil diameter(P<0.05). The 95% limit of agreement(95%LoA)of the measurements of higher-order aberration, including the third-order aberrations at 4mm pupil diameter and the third-order and fourth-order aberrations at 6mm pupil diameter(except for the Z-24)were greater than 0.1μm. The concordance correlation coefficient(Pc)was lower than 0.90, indicating a poor consistency. The correlation coefficients of corneal higher-order aberrations were significantly different among the three aberrometers at 4 and 6mm pupil diameter(r4mm=0.215～0.805, P4mm<0.05; r6mm=0.561～0.916, P6mm<0.001).CONCLUSION:There were significant differences in the measurements of the third- and fourth-order corneal aberrations at 4 and 6mm pupil diameter among Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, and the agreements were poor, so they are not interchangeably in clinical applications.